Spatio-temporal analysis of hematopoietic stem cell dynamics through visualization and manipulation of bone marrow oxygen environment
| Project/Area Number |
20K21621
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Takubo Keiyo 国立研究開発法人国立国際医療研究センター, 研究所, 生体恒常性プロジェクト長 (50502788)
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 造血幹細胞 / 幹細胞ニッチ / 骨髄 / イメージング / メタボロミクス / 低酸素 / 微小循環 / in vivoイメージング / 画像解析 |
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| Outline of Research at the Start |
本研究では骨髄内の酸素分圧の可視化と局所操作技術を確立し、骨髄の酸素分布を解明し、酸素動態が造血幹細胞の運命に及ぼす影響を解析する。具体的にはまず、骨髄の各種細胞の可視化系を多光子レーザー顕微鏡によるin vivoイメージング技術を用いて確立し、次いで酸素分圧分布をりん光プローブを用いて可視化し、さらには骨髄へ薬剤を直接送達する技術を高精細化して酸素分圧を局所操作する技術を確立した上で、造血幹細胞への影響を明らかにする。
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| Outline of Final Research Achievements |
The oxygen environment of bone marrow maintains hematopoietic stem cells and sustains blood cell production. In this study, we used multiphoton laser microscopy, intravital staining, and genetic reporter animals to enable in vivo imaging of living bone marrow with landmarks. In particular, we analyzed the oxygen distribution in the bone marrow and how it changes. Furthermore, the TCA method, a technique for local manipulation of oxygen distribution in bone marrow, was utilized to verify whether changes in hematopoietic stem cells and hematopoiesis occurred.
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| Academic Significance and Societal Importance of the Research Achievements |
In vivoイメージング技術は、生体臓器内の細胞の“生きざま”を直接観察する手法であり、各細胞の時空間動態や、細胞間相互作用を明らかにできる。本研究でin vivoイメージング技術をすべての血液細胞を生み出す造血幹細胞とその近傍のニッチの研究分野に導入し、酸素分圧との同時イメージングが可能となった。今後は骨髄内の細胞社会で生じる各種のイベントや、疾患・病態における変容を高い時空間解像度で検出可能になることが期待される。
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] Characterization of genetically modified mice for phosphoglycerate mutase, a vitally-essential enzyme in glycolysis2021
Author(s)
Mikawa T, Shibata E, Shimada M, Ito K, Ito T, Kanda H, Takubo K, Shimada A, Lleonart ME, Inagaki N, Yokode M, Kondoh H
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Journal Title
PLoS One
Volume: 16
Issue: 4
Pages: e0250856-e0250856
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Obesity accelerates hair thinning by stem cell-centric converging mechanisms2021
Author(s)
Morinaga H, Mohri Y, Grachtchouk M, Asakawa K, Matsumura H, Oshima M, Takayama N, Kato T, Nishimori Y, Sorimachi Y,?Takubo K, Suganami T, Iwama A, Iwakura Y, Dlugosz AA, Nishimura EK.
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Journal Title
Nature
Volume: 595
Issue: 7866
Pages: 266-271
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] SLC15A4 mediates M1-prone metabolic shifts in macrophages and guards immune cells from metabolic stress2021
Author(s)
Kobayashi T, Nguyen-Tien D, Sorimachi Y, Sugiura Y, Suzuki T, Karyu H, Shimabukuro-Demoto S, Uemura T, Okamura T, Taguchi T, Ueki K, Kato N, Goda N, Dohmae N,?Takubo K, Suematsu M, Toyama-Sorimachi N.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 118
Issue: 33
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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